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J Cell Sci. 2018 Mar 20;131(6). pii: jcs214411. doi: 10.1242/jcs.214411.

H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells.

Author information

1
Department of Biomedicine and Prevention, Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy.
2
Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, 951-8510 Niigata, Japan.
3
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 630-0192 Nara, Japan.
4
Department of Experimental Medicine and Surgery, Section of Pathological Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy.
5
Division of Oncology Research, Department of Oncology, Mayo Clinic, Rochester, MN 55905 USA.
6
Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
7
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.
8
European Molecular Biology Laboratory (EMBL), 00015 Rome, Italy.
9
Department of Biomedicine and Prevention, Section of Anatomy, University of Rome Tor Vergata, 00133 Rome, Italy marco.barchi@uniroma2.it.

Abstract

In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair and damage response. However, it is not known whether they are also involved in the maintenance of genome integrity in meiosis. By analyzing chromosome dynamics in H2afx-/- spermatocytes, we found that the synapsis of autosomes and X-Y chromosomes was impaired in a fraction of cells. Such defects correlated with an abnormal recombination profile. Conversely, Mdc1 was dispensable for the synapsis of the autosomes and played only a minor role in X-Y synapsis, compared with the action of H2afx This suggested that those genes have non-overlapping functions in chromosome synapsis. However, we observed that both genes play a similar role in the assembly of MLH3 onto chromosomes, a key step in crossover formation. Moreover, we show that H2afx and Mdc1 cooperate in promoting the activation of the recombination-dependent checkpoint, a mechanism that restrains the differentiation of cells with unrepaired DSBs. This occurs by a mechanism that involves P53. Overall, our data show that, in male germ cells, H2afx and Mdc1 promote the maintenance of genome integrity.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Checkpoint; Crossover; H2afx; Mdc1; Meiosis; X-Y

PMID:
29437857
DOI:
10.1242/jcs.214411
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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